• Title, Summary, Keyword: DNA topoisomerase I

Search Result 71, Processing Time 0.048 seconds

Inhibition of DNA Topoisomerase I by Cryptotanshinone from Salvia miltiorrhiza

  • Lee, Dong-Sun;Hong, Soon-Duck
    • Journal of Microbiology and Biotechnology
    • /
    • v.8 no.1
    • /
    • pp.89-91
    • /
    • 1998
  • Cryptotanshinone induced topoisomerase I-mediated DNA cleavage in vitro as strongly as camptothecin, whereas topoisomerase II-mediated DNA cleavage was not induced by this agent. In DNA relaxation assay using calf thymus DNA topoisomerase I and supercoiled pBR322 DNA, cryptotanshinone inhibited topoisomerase I-mediated DNA relaxation in a dose-dependent manner. In unwinding assay, cryptotanshinone ($50{\mu}M$) did not shift the topoisomers of DNA. These results suggest that cryptotanshinone exerted a preferential inhibition of topoisomerase I without intercalating into DNA.

  • PDF

Inhibition of DNA Topoisomerase I by Cyclo(L-Prolyl-L-Phenylalanyl) Isolated from Streptomyces sp. AMLK-335

  • Rhee, Ki-Hyeong
    • Journal of Microbiology and Biotechnology
    • /
    • v.12 no.6
    • /
    • pp.1013-1016
    • /
    • 2002
  • Cyclo(L-prolyl-L-phenylalanyl) [cyclo(pro-phe)] was isolated from Streptomyces sp. AMLK-335 and found to inhibit DNA topoisomerase I activity. In a DNA relaxation assay using supercoiled pBR322 DNA, cyclo(pro-phe) inhibited the DNA topoisomerase activity more strongly than camptothecin, a known topoisomerase inhibitor. However, at a concentration of $10{\mu}M$, cyclo(pro-phe) produced a lower degree of DNA relaxation than camptothecin, therefore, the inhibition of topoisomerase I activity by cyclo(pro-phe) was also found to be dose dependent. Accordingly, the current results suggest that cyclo(pro-phe) may be a novel inhibitor of topoisomerase I.

Parameter Focusing on the Topoisomerase I-inhibition Activities of 1-(2-furyl)-3-phenylpropenone Derivatives (1-(2-furyl)-3-phenylpropenone 유도체의 DNA Topoisomerase I 저해활성에 대한 parameter focusing)

  • 명평근;최수라;성낙도
    • YAKHAK HOEJI
    • /
    • v.44 no.4
    • /
    • pp.358-361
    • /
    • 2000
  • Parameter focusing on the DNA topoisomerase-Iinhibition with X-substituted phenyl substituents in 1-(2-furyl)-3-phenylpropenone derivatives as inhibition material were analyzed. From the basis on the results the inhibition on DNA topoisomerase I suggested that the inhibition activities of X-substituted phenyl substitutents would depend largely on the net charge of $\beta$-carbon atom, LUMO energy (e.v.) and STERIMOL parameter B$_{5}$ (width) of X. Among them, non-substituent (X=H), 1 and 2,2-dichloro substituent, 4 showed the highest DNA topoisomerase-I inhibition activity.y.

  • PDF

Antimutagenic and DNA Topoisomerase I Inhibition Effects of Sarcodon aspratus Extracts (향버섯(Sarcodon aspratus)추출물의 항돌연변이성 및 DNA Topoisomerase I 저해 효과)

  • 배준태;이갑랑
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.29 no.5
    • /
    • pp.917-921
    • /
    • 2000
  • This study was carried out to investigate the effects on the mutagenicity and activity of DNA topoisomerase I of Sarcodon aspratus. Using an Ames mutagenicity test, which has been used to assess both mutagenic and antimutagenic effects of various molecules, it was observed that the methanol extracted fraction and other fractions (prepared in water or ethylacetate) of Sarcodon aspratus showed a significant antimutagenic activity against a mutagenecity induced by both a direct mutagenic agent such as MNNG and an indirect mutagenic agents such as B(a)P and AFB$_1$in Salmonella typhimurium TA98, TA100. Also, the extract and fractions of Sarcodon aspratus were found to have an inhibitory activity on the relaxation process of DNA topoisomerase I.

  • PDF

Effects of Quinolone Derivatives on Topoisomerase II (퀴놀론 유도체의 Topoisomerase II에 대한 효과)

  • Yeon, Seung-Woo;Paek, Nam-Soo;Kim, Tae-Han;Kim, Kee-Won
    • YAKHAK HOEJI
    • /
    • v.40 no.6
    • /
    • pp.697-704
    • /
    • 1996
  • Quinolone derivatives, SJ5b (ethyl 5,12-dihydro-5-dihydro-5-oxobenzoxazolo[3,2-a]quinoline-6-carboxylate) and SQ7b (3-fluoro-2-(4-methylpiperazin-1-yl)-5.12-dihydro-5-oxobenzoxa zolo[3,2-a]quinoloine carboxylic acid) showed in vitro cytotoxicities against various tumor cell lines. SJ5b and SQ7b completely inhibited the DNA relaxation activities of human placental topoisomerase II at the concentration of 15.63 and 1.95 ${\mu}$g/ml, respectively. However, unlike etoposide which stabilize the topoisomerase II-DNA complex, SQ7b did not cause topoisomerase II-mediated DNA cleavage and SJ5b weakly stabilized the topoisomerase II-DNA cleavable complex. Through both experiments. DNA relaxation assay by the increment of topoisomerase II concentration and DNA unwinding assay, it was shown that SJ5b and SQ7b did not interact with topoisomerase II itself but bound to DNA. Therefore, it was concluded that DNA binding of SJ5b and SQ7b caused the inhibition of topoisomerase II related to DNA relaxation but no or very weak stabilization of topoisomerase II-DNA cleavable complex. In addition, SJ5b and SQ7b prevented whole cell nucleic acid syntheses in HL60 cells.

  • PDF

Effects of camptothecin on the expression of DNA topoisomerase I and c-myc in HL-60 human leukemia cells (HL-60 사람 백혈병 세포에서 camptothecin이 DNA topoisomerase l과 c-myc의 발현에 미치는 영향)

  • 정인철;정대성;류경자;박장수;조무연
    • Journal of Life Science
    • /
    • v.10 no.6
    • /
    • pp.621-629
    • /
    • 2000
  • Camptothecin (CPT) is an antitumor alkaloid that has been isolated from the Chinese tree, Camptotheca acuminata. The cytotoxicity of CPT has been correlated to its inhibition of DNA topoisomerase (Topo) I by stabilizing drug-enzyme-DNA “cleavable complex" resulting in DNA single-strand breaks and DNA-protein crosslinks. This studies were designed to elucidate whether CPT regulates Topo I mediated by CPT in DNAs containing c-myc protooncogene. We have conducted experiments on Topo I purification, pUC-MYC I cloning and Topo I assay using electrophoresis, quantitative RT-PCR and Northern blotting techniques. CPT ingibited the relaxation activity of Topo I in pUC19 DNA at various concentrations (1-1000 $\mu$M), while it enhanced the cleavage of Topo I in the pUC-MYC I by forming a cleavable complex at relatively high concentrations (100-1000 $\mu$M). In HL-60 cells treated with CPT, the expression of c-myc gene was decreased over that in the control group with no changes in the expression of Topo I mRNA. Our results suggest that Topo I is the target of CPT cytotoxicity but it does not affect Topo I extression, and the suppression of c-myc mRNA expression by CPT is due to c-myc damage resulted from formation of a cleavable complex with CPT. CPT.

  • PDF

Inhibition Mode of DNA Topoisomerase by Dibutyl Phthalate

  • Lee, Dong-Sun;Hong, Soon-Duck
    • Journal of Microbiology and Biotechnology
    • /
    • v.6 no.5
    • /
    • pp.366-367
    • /
    • 1996
  • Dibutyl phthalate induced topoisomerase Ⅰ mediated DNA relaxation comparable to that of camptothecin, and topoisomerase Ⅱ mediated DNA relaxation equipotent to that of 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA). The relaxation activities of dibutyl phthalate were dose-de-pendent and nearly as potent as those of camptothecin and m-AMSA.

  • PDF

2- or 6-(1-Azidoalkyl)-5,8-Dimethoxy-1,4-Napyhthoquinone: Synthesis, Evaluation of Cytotoxic Activity, Antitumor Activity and Inhibitory Effect on DNA Topoisomerase-I

  • Chae, Gyu-Han;Song, Gyu-Yong;Kim, Yong;Cho, Hoon;Sok, Dai-Eun;Ahn, Byung-Zun
    • Archives of Pharmacal Research
    • /
    • v.22 no.5
    • /
    • pp.507-514
    • /
    • 1999
  • 6-(1-azidoalkyl)-DMNQ derivatives compared to 2-(1-azidoalkyl)-DMNQ isomers, exhibited higher cytotoxic activity against L1210 mouse leukemia cells and stronger inhibition of DNA topoisomerase-I (TOPO-I), suggesting involvement of steric hindrance. However, similar antitumor activity against mice bearing S-180 cell was shown by 2-an 6-(1-azidoalkyl)-DMNQ derivatives.

  • PDF

Da-125 a New Antitumor Agent, Inhibits Topoisomerase II as Topoisomerase Poison and DNA Intercalator Simultaneously

  • Seo, Jin-Wook;Lee, Hak-Sung;Lee, Min-Jun;Kim, Mi-Ra;Shin, Cha-Gyun
    • Archives of Pharmacal Research
    • /
    • v.27 no.1
    • /
    • pp.77-82
    • /
    • 2004
  • DA-125, a novel derivative of adriamycin, is known for its anti-cancer activity. In this study, the inhibitory mechanism of DA-125 on topoisomerase was investigated in the simian virus 40 (SV40) replicating CV-1 cell by studying the SV40 DNA replication intermediates and DNA-topoisomerase complexes. DNA-protein complexes that were formed in the drug-treated cells were quantitated by using a glass filter assay. SV40 DNA replication intermediates that were accumulated in the drug-treated CV-1 cell were analyzed in a high resolution gel. DA-125 did not accumulate B-dimers of SV40 DNA replication intermediates which were found in the adriamycin-treated CV-1 cells. DA-125 induced a dose-dependent formation of the DNA-protein complexes, while adriamycin did not. When adriamycin and etoposide (VP16) were added to the SV40-infected cells at the same time, adriamycin blocked the formation of the DNA-protein complexes induced by VP16 in a dose-dependent manner. However, DA-125 blocked the formation of the DNA-protein complexes induced by VP16 up to the maximum level of the DNA-protein complexes that were induced by DA-125 alone. Adriamycin and DA-125 did not inhibit the formation of the DNA-protein complexes that were caused by camptothecin, a known topoisomerase I poison. DA-125 is bifunctional in inhibiting topoisomerase II because it simultaneously has the properties of the topoisomerase II poison and the DNA intercalator. As a topoisomerase II poison, DA-125 alone induced dose-dependent formation of the DNA-protein complexes. However, as a DNA intercalator, it quantitatively inhibited the formation of the DNA-protein complexes induced by a strong topoisomerase II poison VP16. Furthermore considering that the levels of the DNA-protein complex induced by VP16 were decreased by DA-125 in terms of the topoisomerase II poison, we suggest that DA-125 has a higher affinity to the drug-binding sites of DNA than VP16 has.

DNA Toposiomerase I Inhibitor by Streptomyces sp. 7489 (방선균주 7489가 생산하는 DNA Topoisomerase I 저해제에 관한 연구)

  • Lee, Dong-Sun;Ha, Sang-Chul;Lee, Sang-Yong;Kim, Jong-Guk;Hong, Soon-Duck
    • Microbiology and Biotechnology Letters
    • /
    • v.24 no.1
    • /
    • pp.101-104
    • /
    • 1996
  • During the screening of inhibitor of DNA topoisomerase I from microbial secondary metabolites, Streptomyces melanosporofaciens 7489 which was capable of producing high level of inhibitor was selected from soil. The active compound (7489-1) was purified from the culture broth by solvent extraction, silica gel column chromatography and HPLC. The inhibitor was identified as dibutyl phthalate by spectroscopic methods of UV, $^{1}H$-NMR, $^{13}C$-NMR, DEPT and EI-MS. 7489-1 showed a strong inhibitory activity against topoisomerase I with 10 ${\mu}$M of $IC_{50}$ value.

  • PDF